Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease characterized by the gradual destruction of the insulin-producing pancreatic islet .beta.-cells. Clinical symptoms of diabetes set in at a fairly late stage of this process, at a point where about 90% of the .beta.-cells have been destroyed. However, in recent years it has been found that a number of circulating autoantibodies against .beta.-cells associated with IDDM are present in serum before the clinical onset of the disease. Such circulating autoantibodies include one against a 64 kD islet .beta.-cell autoantigen (S. Baekkeskov et al., Nature 298, 1982, pp. 167-169). The 64 kD autoantibody has been found to be present in the serum of more than 80% of the patients with newly diagnosed IDDM and has furthermore been found in serum up to several years before the clinical onset of the disease (S. Baekkeskov et al., J. Clin. Invest. 79, 1987, pp. 926-934; M. R. Atkinson et al., Lancet 335, 1990, pp. 1357-1360; E. Sigurdsson and S. Baekkeskov, Curr. Top. Microbiol. Immun. 164, 1990, pp. 143-167). The early detection of the 64 kD autoantibody would be of great value for the study of the development of IDDM as well as for devising preventive therapies.
The 64 kD autoantigen has been identified (S. Baekkeskov et al., Nature 347, 1990, pp. 151-156) as the enzyme glutamic acid decarboxylase (GAD) which is otherwise known to be involved in the biosynthesis of gamma-amino butyric acid in the central nervous system. The use of GAD for the diagnosis of preclinical IDDM has been suggested in WO 92/04632 and WO 92/05446.
A 38 kD .beta.-cell antigen recognised by a T cell clone isolated from the blood of a recently diagnosed IDDM patient is described in WO 91/17186. It is suggested to use the antigen in the diagnosis or therapy of IDDM.